Characterization of an Acinetobacter baumannii lptD deletion strain: Permeability defects and response to inhibition of lipopolysaccharide and fatty acid biosynthesis

Journal of Bacteriology

Volumn 198, Issue 4, 2016, Pages 731-741

  Bojkovic, Jade ^a   Richie, Daryl L ^a   Six, David A ^a   Rath, Christopher M ^a   Sawyer, William S ^a   Hu, Qijun ^a   Dean, Charles R ^a  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTIBIOTIC AGENT; GLUCOSAMINE DERIVATIVE; LIPID A; LIPOPOLYSACCHARIDE; N PHENYL 1 NAPHTHYLAMINE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE; URIDINE DIPHOSPHATE 3 O 3 HYDROXYLAUROYL N ACETYL ALPHA DEXTRO GLUCOSAMINE; FATTY ACID; OUTER MEMBRANE PROTEIN;

ACINETOBACTER BAUMANNII; ARTICLE; BACTERIAL GROWTH; BACTERIAL MEMBRANE; BIOACCUMULATION; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; DELETION MUTANT; ENZYME INHIBITION; FATTY ACID SYNTHESIS; FLUORESCENCE ANALYSIS; GENE TRANSLOCATION; HYDROPHOBICITY; LIPID ANALYSIS; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; OUTER MEMBRANE; PRIORITY JOURNAL; SENSITIVITY ANALYSIS; BIOSYNTHESIS; CELL MEMBRANE; GENE DELETION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PERMEABILITY; TRANSPORT AT THE CELLULAR LEVEL;

ACINETOBACTER BAUMANNII; BACTERIAL OUTER MEMBRANE PROTEINS; BIOLOGICAL TRANSPORT; CELL MEMBRANE; FATTY ACIDS; GENE DELETION; GENE EXPRESSION REGULATION, BACTERIAL; LIPOPOLYSACCHARIDES; PERMEABILITY;

EID: 84958069216     PISSN: 00219193     EISSN: 10985530     Source Type: Journal    
DOI: 10.1128/JB.00639-15     Document Type: Article

References (62)

1. Whitfield C, Trent MS. 2014. Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem 83:99-128. http://dx.doi.org/10.1146/annurev-biochem-060713-035600.
2. Raetz CR, Whitfield C. 2002. Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635-700. http://dx.doi.org/10.1146/annurev.biochem.71.110601.135414.
3. Clements JM, Coignard F, Johnson I, Chandler S, Palan S, Waller A, Wijkmans J, Hunter MG. 2002. Antibacterial activities and characterization of novel inhibitors of LpxC. Antimicrob Agents Chemother 46:1793-1799. http://dx.doi.org/10.1128/AAC.46.6.1793-1799.2002.
4. Bodewits K, Raetz CR, Govan JR, Campopiano DJ. 2010. Antimicrobial activity of CHIR-090, an inhibitor of lipopolysaccharide biosynthesis, against the Burkholderia cepacia complex. Antimicrob Agents Chemother 54:3531-3533. http://dx.doi.org/10.1128/AAC.01600-09.
5. Lee CJ, Liang X, Chen X, Zeng D, Joo SH, Chung HS, Barb AW, Swanson SM, Nicholas RA, Li Y, Toone EJ, Raetz CR, Zhou P. 2011. Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design. Chem Biol 18:38-47. http://dx.doi.org/10.1016/j.chembiol.2010.11.011.
6. Brown MF, Reilly U, Abramite JA, Arcari JT, Oliver R, Barham RA, Che Y, Chen JM, Collantes EM, Chung SW, Desbonnet C, Doty J, Doroski M, Engtrakul JJ, Harris TM, Huband M, Knafels JD, Leach KL, Liu S, Marfat A, Marra A, McElroy E, Melnick M, Menard CA, Montgomery JI, Mullins L, Noe MC, O'Donnell J, Penzien J, Plummer MS, Price LM, Shanmugasundaram V, Thoma C, Uccello DP, Warmus JS, Wishka DG. 2012. Potent inhibitors of LpxC for the treatment of Gram-negative infections. J Med Chem 55:914-923. http://dx.doi.org/10.1021/jm2014748.
7. Montgomery JI, Brown MF, Reilly U, Price LM, Abramite JA, Arcari J, Barham R, Che Y, Chen JM, Chung SW, Collantes EM, Desbonnet C, Doroski M, Doty J, Engtrakul JJ, Harris TM, Huband M, Knafels JD, Leach KL, Liu S, Marfat A, McAllister L, McElroy E, Menard CA, Mitton-Fry M, Mullins L, Noe MC, O'Donnell J, Oliver R, Penzien J, Plummer M, Shanmugasundaram V, Thoma C, Tomaras AP, Uccello DP, Vaz A, Wishka DG. 2012. Pyridone methylsulfone hydroxamate LpxC inhibitors for the treatment of serious gram-negative infections. J Med Chem 55:1662-1670. http://dx.doi.org/10.1021/jm2014875.
8. Warmus JS, Quinn CL, Taylor C, Murphy ST, Johnson TA, Limberakis C, Ortwine D, Bronstein J, Pagano P, Knafels JD, Lightle S, Mochalkin I, Brideau R, Podoll T. 2012. Structure based design of an in vivo active hydroxamic acid inhibitor of P. aeruginosa LpxC. Bioorg Med Chem Lett 22:2536-2543. http://dx.doi.org/10.1016/j.bmcl.2012.01.140.
9. Liang X, Lee CJ, Chen X, Chung HS, Zeng D, Raetz CR, Li Y, Zhou P, Toone EJ. 2011. Syntheses, structures and antibiotic activities of LpxC inhibitors based on the diacetylene scaffold. Bioorg Med Chem 19:852-860. http://dx.doi.org/10.1016/j.bmc.2010.12.017.
10. Jenkins RJ, Dotson GD. 2012. Dual targeting antibacterial peptide inhibitor of early lipid A biosynthesis. ACS Chem Biol 7:1170-1177. http://dx.doi.org/10.1021/cb300094a.
11. Jenkins RJ, Heslip KA, Meagher JL, Stuckey JA, Dotson GD. 2014. Structural basis for the recognition of peptide RJPXD33 by acyltransferases in lipid A biosynthesis. J Biol Chem 289:15527-15535. http://dx.doi.org/10.1074/jbc. M114.564278.
12. Nayar AS, Dougherty TJ, Ferguson KE, Granger BA, McWilliams L, Stacey C, Leach LJ, Narita S, Tokuda H, Miller AA, Brown DG, McLeod SM. 2015. Novel antibacterial targets and compounds revealed by a highthroughput cell wall reporter assay. J Bacteriol 197:1726-1734. http://dx.doi.org/10.1128/JB.02552-14.
13. Werneburg M, Zerbe K, Juhas M, Bigler L, Stalder U, Kaech A, Ziegler U, Obrecht D, Eberl L, Robinson JA. 2012. Inhibition of lipopolysaccharide transport to the outer membrane in Pseudomonas aeruginosa by peptidomimetic antibiotics. Chembiochem 13:1767-1775. http://dx.doi.org/10.1002/cbic.201200276.
14. Srinivas N, Jetter P, Ueberbacher BJ, Werneburg M, Zerbe K, Steinmann J, Van der Meijden B, Bernardini F, Lederer A, Dias RL, Misson PE, Henze H, Zumbrunn J, Gombert FO, Obrecht D, Hunziker P, Schauer S, Ziegler U, Kach A, Eberl L, Riedel K, DeMarco SJ, Robinson JA. 2010. Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science 327:1010-1013. http://dx.doi.org/10.1126/science.1182749.
15. Schmidt J, Patora-Komisarska K, Moehle K, Obrecht D, Robinson JA. 2013. Structural studies of beta-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp. Bioorg Med Chem 21:5806-5810. http://dx.doi.org/10.1016/j.bmc.2013.07.013.
16. Montefour K, Frieden J, Hurst S, Helmich C, Headley D, Martin M, Boyle DA. 2008. Acinetobacter baumannii: an emerging multidrugresistant pathogen in critical care. Crit Care Nurse 28:15-25.
17. Zavascki AP, Carvalhaes CG, Picao RC, Gales AC. 2010. Multidrugresistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy. Expert Rev Anti Infect Ther 8:71-93. http://dx.doi.org/10.1586/eri.09.108.
18. Gordon NC, Wareham DW. 2010. Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and resistance. Int J Antimicrob Agents 35:219-226. http://dx.doi.org/10.1016/j.ijantimicag.2009.10.024.
19. Manchanda V, Sanchaita S, Singh NP. 2010. Multidrug resistance Acinetobacter. J Glob Infect Dis 2:291-304. http://dx.doi.org/10.4103/0974-777X.68538.
20. Falagas ME, Bliziotis IA. 2007. Pandrug-resistant Gram-negative bacteria: the dawn of the post-antibiotic era? Int J Antimicrob Agents 29:630-636. http://dx.doi.org/10.1016/j.ijantimicag.2006.12.012.
21. Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, Dhanji H, Chart H, Bou G, Livermore DM, Woodford N. 2011. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother 55:3370-3379. http://dx.doi.org/10.1128/AAC.00079-11.
22. Moffatt JH, Harper M, Harrison P, Hale JD, Vinogradov E, Seemann T, Henry R, Crane B, St Michael F, Cox AD, Adler B, Nation RL, Li J, Boyce JD. 2010. Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother 54:4971-4977. http://dx.doi.org/10.1128/AAC.00834-10.
23. Moffatt JH, Harper M, Adler B, Nation RL, Li J, Boyce JD. 2011. Insertion sequence ISAba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii. Antimicrob Agents Chemother 55:3022-3024. http://dx.doi.org/10.1128/AAC.01732-10.
24. Beceiro A, Moreno A, Fernandez N, Vallejo JA, Aranda J, Adler B, Harper M, Boyce JD, Bou G. 2014. Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii. Antimicrob Agents Chemother 58:518-526. http://dx.doi.org/10.1128/AAC.01597-13.
25. Steeghs L, den Hartog R, den Boer A, Zomer B, Roholl P, van der Ley P. 1998. Meningitis bacterium is viable without endotoxin. Nature 392: 449-450. http://dx.doi.org/10.1038/33046.
26. Peng D, Hong W, Choudhury BP, Carlson RW, Gu XX. 2005. Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate. Infect Immun 73:7569-7577. http://dx.doi.org/10.1128/IAI.73.11.7569-7577.2005.
27. de Berardinis V, Vallenet D, Castelli V, Besnard M, Pinet A, Cruaud C, Samair S, Lechaplais C, Gyapay G, Richez C, Durot M, Kreimeyer A, Le Fevre F, Schachter V, Pezo V, Doring V, Scarpelli C, Medigue C, Cohen GN, Marliere P, Salanoubat M, Weissenbach J. 2008. A complete collection of single-gene deletion mutants of Acinetobacter baylyi ADP1. Mol Syst Biol 4:174. http://dx.doi.org/10.1038/msb.2008.10.
28. Zhang G, Meredith TC, Kahne D. 2013. On the essentiality of lipopolysaccharide to Gram-negative bacteria. Curr Opin Microbiol 16:779-785. http://dx.doi.org/10.1016/j.mib.2013.09.007.
29. Bartling CM, Raetz CR. 2008. Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis. Biochemistry 47: 5290-5302. http://dx.doi.org/10.1021/bi800240r.
30. Karow M, Fayet O, Georgopoulos C. 1992. The lethal phenotype caused by null mutations in the Escherichia coli htrB gene is suppressed by mutations in the accBC operon, encoding two subunits of acetyl coenzyme A carboxylase. J Bacteriol 174:7407-7418.
31. Zeng D, Zhao J, Chung HS, Guan Z, Raetz CR, Zhou P. 2013. Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis. J Biol Chem 288:5475-5486. http://dx.doi.org/10.1074/jbc. M112.447607.
32. Yao Z, Davis RM, Kishony R, Kahne D, Ruiz N. 2012. Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli. Proc Natl Acad Sci U S A 109:E2561-E2568. http://dx.doi.org/10.1073/pnas.1209742109.
33. Steeghs L, de Cock H, Evers E, Zomer B, Tommassen J, van der Ley P. 2001. Outer membrane composition of a lipopolysaccharide-deficient Neisseria meningitidis mutant. EMBO J 20:6937-6945. http://dx.doi.org/10.1093/emboj/20.24.6937.
34. Rampersad SN. 2012. Multiple applications of Alamar Blue as an indicator of metabolic function and cellular health in cell viability bioassays. Sensors (Basel) 12:12347-12360. http://dx.doi.org/10.3390/s120912347.
35. Caughlan RE, Jones AK, Delucia AM, Woods AL, Xie L, Ma B, Barnes SW, Walker JR, Sprague ER, Yang X, Dean CR. 2012. Mechanisms decreasing in vitro susceptibility to the LpxC inhibitor CHIR-090 in the Gram-negative pathogen Pseudomonas aeruginosa. Antimicrob Agents Chemother 56:17-27. http://dx.doi.org/10.1128/AAC.05417-11.
36. Aranda J, Poza M, Pardo BG, Rumbo S, Rumbo C, Parreira JR, Rodriguez-Velo P, Bou G. 2010. A rapid and simple method for constructing stable mutants of Acinetobacter baumannii. BMC Microbiol 10:279. http://dx.doi.org/10.1186/1471-2180-10-279.
37. Davis MR, Jr, Goldberg JB. 28 May 2012. Purification and visualization of lipopolysaccharide from Gram-negative bacteria by hot aqueousphenol extraction. J Vis Exp http://dx.doi.org/10.3791/3916.
38. Loh B, Grant C, Hancock RE. 1984. Use of the fluorescent probe 1-N-phenylnaphthylamine to study the interactions of aminoglycoside antibiotics with the outer membrane of Pseudomonas aeruginosa. Antimicrob Agents Chemother 26:546-551. http://dx.doi.org/10.1128/AAC.26.4.546.
39. Oliva B, O'Neill AJ, Miller K, Stubbings W, Chopra I. 2004. Antistaphylococcal activity and mode of action of clofazimine. J Antimicrob Chemother 53:435-440. http://dx.doi.org/10.1093/jac/dkh114.
40. Bakshi S, Choi H, Rangarajan N, Barns KJ, Bratton BP, Weisshaar JC. 2014. Nonperturbative imaging of nucleoid morphology in live bacterial cells during an antimicrobial peptide attack. Appl Environ Microbiol 80: 4977-4986. http://dx.doi.org/10.1128/AEM.00989-14.
41. BiggerstaffJP, Le Puil M, Weidow BL, Prater J, Glass K, Radosevich M, White DC. 2006. New methodology for viability testing in environmental samples. Mol Cell Probes 20:141-146. http://dx.doi.org/10.1016/j.mcp.2005.11.006.
42. Bos MP, Tefsen B, Geurtsen J, Tommassen J. 2004. Identification of an outer membrane protein required for the transport of lipopolysaccharide to the bacterial cell surface. Proc Natl Acad Sci U S A 101:9417-9422. http://dx.doi.org/10.1073/pnas.0402340101.
43. Wang X, Quinn PJ. 2010. Lipopolysaccharide: biosynthetic pathway and structure modification. Prog Lipid Res 49:97-107. http://dx.doi.org/10.1016/j.plipres.2009.06.002.
44. Emiola A, George J, Andrews SS. 2014. A complete pathway model for lipid A biosynthesis in Escherichia coli. PLoS One 10:e0121216. http://dx.doi.org/10.1371/journal.pone.0121216.
45. Brozek KA, Hosaka K, Robertson AD, Raetz CR. 1989. Biosynthesis of lipopolysaccharide in Escherichia coli. Cytoplasmic enzymes that attach 3-deoxy-D-manno-octulosonic acid to lipid A. J Biol Chem 264:6956-6966.
46. Clementz T, Raetz CR. 1991. A gene coding for 3-deoxy-D-mannooctulosonic-acid transferase in Escherichia coli. Identification, mapping, cloning, and sequencing. J Biol Chem 266:9687-9696.
47. Belunis CJ, Raetz CR. 1992. Biosynthesis of endotoxins. Purification and catalytic properties of 3-deoxy-D-manno-octulosonic acid transferase from Escherichia coli. J Biol Chem 267:9988-9997.
48. Delucia AM, Six DA, Caughlan RE, Gee P, Hunt I, Lam JS, Dean CR. 2011. Lipopolysaccharide (LPS) inner-core phosphates are required for complete LPS synthesis and transport to the outer membrane in Pseudomonas aeruginosa PAO1. mBio 2:e00142-11. http://dx.doi.org/10.1128/mBio.00142-11.
49. Rao NN, Gomez-Garcia MR, Kornberg A. 2009. Inorganic polyphosphate: essential for growth and survival. Annu Rev Biochem 78:605-647. http://dx.doi.org/10.1146/annurev.biochem.77.083007.093039.
50. Alcantara C, Blasco A, Zuniga M, Monedero V. 2014. Accumulation of polyphosphate in Lactobacillus spp. and its involvement in stress resistance. Appl Environ Microbiol 80:1650-1659. http://dx.doi.org/10.1128/AEM.03997-13.
51. Genevrois S, Steeghs L, Roholl P, Letesson JJ, van der Ley P. 2003. The Omp85 protein of Neisseria meningitidis is required for lipid export to the outer membrane. EMBO J 22:1780-1789. http://dx.doi.org/10.1093/emboj/cdg174.
52. Barb AW, Jiang L, Raetz CR, Zhou P. 2007. Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: time-dependent inhibition and specificity in ligand binding. Proc Natl Acad Sci U S A 104:18433-18438. http://dx.doi.org/10.1073/pnas.0709412104.
53. McClerren AL, Endsley S, Bowman JL, Andersen NH, Guan Z, Rudolph J, Raetz CR. 2005. A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin. Biochemistry 44:16574-16583. http://dx.doi.org/10.1021/bi0518186.
54. Barb AW, Zhou P. 2008. Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipidAsynthesis. Curr Pharm Biotechnol 9:9-15. http://dx.doi.org/10.2174/138920108783497668.
55. Barb AW, McClerren AL, Snehelatha K, Reynolds CM, Zhou P, Raetz CR. 2007. Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli. Biochemistry 46:3793-3802. http://dx.doi.org/10.1021/bi6025165.
56. Vance D, Goldberg I, Mitsuhashi O, Bloch K. 1972. Inhibition of fatty acid synthetases by the antibiotic cerulenin. Biochem Biophys Res Commun 48:649-656. http://dx.doi.org/10.1016/0006-291X(72)90397-X.
57. D'Agnolo G, Rosenfeld IS, Awaya J, Omura S, Vagelos PR. 1973. Inhibition of fatty acid synthesis by the antibiotic cerulenin. Specific inactivation of beta-ketoacyl-acyl carrier protein synthetase. Biochim Biophys Acta 326:155-156.
58. Kawaguchi A, Tomoda H, Nozoe S, Omura S, Okuda S. 1982. Mechanism of action of cerulenin on fatty acid synthetase. Effect of cerulenin on iodoacetamide-induced malonyl-CoA decarboxylase activity. J Biochem 92:7-12.
59. Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO. 2001. Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J Biol Chem 276:6551-6559. http://dx.doi.org/10.1074/jbc. M007101200.
60. Cipolla L, Polissi A, Airoldi C, Gabrielli L, Merlo S, Nicotra F. 2011. New targets for antibacterial design: Kdo biosynthesis and LPS machinery transport to the cell surface. Curr Med Chem 18:830-852. http://dx.doi.org/10.2174/092986711794927676.
61. Singh SB, Dayananth P, Balibar CJ, Garlisi CG, Lu J, Kishii R, Takei M, Fukuda Y, Ha S, Young K. 2015. Kibdelomycin is a bactericidal broadspectrum aerobic antibacterial agent. Antimicrob Agents Chemother 59: 3474-3481. http://dx.doi.org/10.1128/AAC.00382-15.
62. Bojkovic J, Rath C, Richie DL, Sawyer W, Six DA, Dean CR. 2015. Characterization of an A. baumannii lptD deletion strain: permeability defects and response to inhibition of LpxC, poster 2112. Abstr 115th Gen Meet Am Soc Microbiol. American Society for Microbiology, Washington, DC.